Objective To investigate the relationship between the expression levels of serum microRNA-181a(miR-181a)and sphingosine 1-phosphate receptor 1(S1PR1)messenger RNA(mRNA)and the occur-rence of acute exacerbation in patients with bronchial asthma.Methods From January 2021 to May 2023,a to-tal of 132 patients with bronchial asthma in acute exacerbation stage from Shijiazhuang Emergency Center were selected as the acute stage group,89 patients with bronchial asthma in remission stage were selected as the remission stage group and 90 healthy personnel for physical examination were selected as the control group.The acute stage group was divided into mild group(50 cases),moderate group(45 cases)and severe group(37 cases).Clinical data were collected and pulmonary function[ratio of forced expiratory volume to forced vital capacity in the first second(FEV1/FVC)and percentage of peak expiratory flow rate to expected value(PEF％pred)]was examined.Real-time fluorescence quantitative PCR was used to detect the serum miR-181a and S1PR1 mRNA expression.Pearson method was used to analyze the correlation between serum miR-181a and S1PR1 mRNA and lung function indicators in patients with acute exacerbation of bronchial asthma.Multivariate Logistic regression analysis was used to identify factors affecting the occurrence of acute exacerbation in patients with bronchial asthma.Receiver operating characteristic(ROC)curve was used to e-valuate the value of serum miR-181a and S1PR1 mRNA in predicting the occurrence of acute exacerbation in patients with bronchial asthma.Results The FEV1/FVC,PEF％pred and relative expression level of serum miR-181a in control group,remission stage group and acute stage group were decreased successively,while the relative expression level of S1PR1 mRNA were increased successively(P＜0.05).The relative expression lev-el of serum miR-181a in mild group,moderate group and severe group was decreased successively,and the rel-ative expression level of S1PR1 mRNA was increased successively(P＜0.05).In patients with acute exacer-bation of bronchial asthma,serum miR-181a and S1PR1 mRNA were negatively correlated(P＜0.05),serum miR-181a was positively correlated with FEV1/FVC,PEF％pred(P＜0.05),and serum S1PR1 mRNA was negatively correlated with FEV1/FVC,PEF％pred(P＜0.05).Low level of FEV1/FVC,low level of PEF％pred,low relative expression level of miR-181a and high relative expression level of S1PR1 mRNA were inde-pendent risk factors affecting the occurrence of acute exacerbation in patients with bronchial asthma(P＜0.05).The area under the curve(AUC)of the combination of serum miR-181a and S1PR1 mRNA for predic-ting the acute exacerbation in patients with bronchial asthma was 0.890,which was higher than the AUC of the two predicted alone(P＜0.05).Conclusion The serum miR-181a in patients with bronchial asthma is lowly expressed,while S1PR1 mRNA is highly expressed.Both are related to the occurrence and severity of acute exacerba-tion as well as lung function,and have high predictive efficacy for the occurrence of acute exacerbation.

Thyroid carcinoma is a common malignant tumor of the endocrine system and its incidence has increased significantly in recent years. Surgery is the most important initial treatment for thyroid cancer, but total thyroidectomy increases the risk of postoperative hyponatremia and recurrent laryngeal nerve injury while prolonging the disease-free survival of patients, decreasing the risk of disease recurrence and reducing residual lesions. Therefore, how to make the best surgical decision based on preoperative findings is still controversial. V-raf murine sarcoma viral oncogene homolog B1 ( BRAF), as one of the common genetic mutations in thyroid malignant tumors, is closely related to the degree of malignancy and prognosis of the tumor. Preoperative BRAF gene testing can help determine the aggressive pathological features of thyroid tumors and provide scientific guidance for clinicians to decide the scope of surgical resection.This article reviews the guiding role of BRAF gene mutation detection results in total thyroid cancer resection.

With the growing demand for facial aesthetics,facial asymmetry has emerged as a prominent clinical concern.Skeletal Class Ⅲ malocclusion could not only affect facial aesthetics,but also have an adverse effect on oral function.Facial asymmetry is caused by complex factors and can manifest in various ways,including morphological asymmetry of the maxillofacial unit,positional asymmetry of maxillofacial units,and transverse dentition compensation.Therefore,comprehensive classification based on maxillofacial features of facial asymmetry is crucial for diagnosis,treatment,and surgical planning.This article aims to review recent progress of re-search on the maxillofacial features,classification,and treatment of skeletal Class Ⅲ malocclusion with facial asymmetry,in order to provide reference for clinical diagnosis and treatment.

Objective:To explore the diagnostic efficacy difference and clinical diagnostic value of chronic lymphocytic leukemia flow (CLLflow) score and Moreau score (MS) in the diagnosis of chronic lymphocytic leukemia (CLL).Methods:According to the latest international and national diagnosis criteria for CLL, 133 patients with B-cell chronic lymphoproliferative diseases and uncertain immunophenotypes (B-CLPD), diagnosed by Zhengzhou Jinyu Comprehensive Haematological Pathology Diagnosis Centre from March 2020 to May 2021, were included in this study. Above patients were divided into the CLL group ( n=83) and non-CLL group ( n=50). The expression of clusters of differentiation (CD)5, CD10, CD20, CD19, κ light chain, λ light chain, FMC7, CD23, CD22, surface immunoglobulin M, CD200 and CD79 were detected by flow cytometry, and CLLflow score and MS score were calculated respectively according to the scoring rules. A fourfold table was used to compare the diagnostic efficacy of the two scoring systems, and the Kappa test and McNemar test were used to compare the consistency and superiority of the systems. Results:The rate of negative and positive CLLflow score were 4.8% (4/83) and 95.2% (79/83) in the CLL group and were 80.0% (40/50) and 20.0% (10/50) in the non-CLL group, and respectively (both P<0.001). The MS score (≤2, =3 and≥4) was 1.2% (1/83), 10.8% (9/83) and 88.0% (73/83) in the CLL group and was 86.0% (43/50), 14.0% (7/50) and 0 in the non-CLL group, there were significant statistical difference between the two groups ( P<0.001). The sensitivity, specificity, positive predictive value and negative predictive value of the CLLflow score were 95.2% (79/83), 80.0% (40/50), 88.8% (79/89) and 90.9% (40/44), respectively and those of MS score were 98.8% (82/83), 86.0% (43/50), 92.1% (82/89) and 97.7% (43/44) respectively. The overall coincidence rate, positive and negative coincidence rate between the CLLflow score and MS score were 91.0% (121/133), 93.3% (83/89) and 86.4% (38/44) respectively. Besides, the McNeamr dominance test presented no significant difference ( P>0.05) and high consistency (Kappa=0.796) between the two scoring systems. With MS≤2 and MS≥4, the sensitivity and the specificity of the MS score were 100% (73/73) and 97.7% (43/44) respectively, and for the CLLflow score, the sensitivity and the specificity were 97.3% (71/73) and 86.4% (38/44) in this MS range. With MS = 3, the sensitivity and specificity of the MS score were 100% (9/9) and 0 (0/7), and CLLflow was 88.9% (8/9) and 57.1% (4/7). Conclusions:The diagnostic efficacy is similar and presents high consistency between the CLLflow score and MS score in CLL diagnosis. For CLL patients with MS = 3, the specificity of MS is relatively low, combined assessment with CLLflow score could improve the diagnosis efficacy for CLL in these patients.

OBJECTIVE To explore the pricing methods of multi-indication drugs suitable for China from the economic perspective. METHODS By sorting out the situation and pricing methods of multi-indication drugs in China’s health insurance negotiation in recent years， the experience of typical countries （Sweden， Germany， Britain， Italy， etc.） in the value measurement， access and management of multi-indication drugs were explored with 3 methods， namely， branded pricing， weighted average bidding pricing， and single bidding pricing under the risk sharing agreement. The advantages and disadvantages of the 2 types of multi-indication drug pricing methods， such as single bidding pricing and indication-based pricing， and conditions of use were explored， so as to put forward a pricing method suitable for multi-indication drugs in China. RESULTS＆＆CONCLUSIONS The pricing of multi-indication drugs by single bidding pricing mode has certain disadvantages at this stage， and should be supplemented and improved by agreement pricing. Based on international experience， China can explore a reasonable management mode of drug indications， adopt a pricing mode with agreement pricing as the main mode and multiple pricing modes as the coexisting mode， and promote the development of pharmacoeconomic evaluation and the improvement of drug use information collection mechanism.

Objective:To analyze and explore the possible mechanism of anti-tumor metastasis of Notoginseng Radix et Rhizoma using Internet pharmacology. Methods:The active components and targets of Notoginseng Radix et Rhizoma were screened by retrieving Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP). GeneCards database was used to screen the anti-tumor metastasis-related targets, and compounds and disease targets were under mapping analysis. Key targets of Notoginseng Radix et Rhizoma for anti-tumor metastasis were screened through Venn map. With the help of Cytoscape 3.7.2 software, a compound-disease network diagram was constructed. String platform was used to build a PPI network. Bioconductor was used to enrich the target genes for KEGG signaling pathway and GO biological process analysis. Results:Totally 119 active components were selected from Notoginseng Radix et Rhizoma. There were 8 eligible active components, corresponding to 162 related targets, 121 targets related to anti-tumor metastasis, and 30 key targets screened by PPI network, including AKT1, MAPK1, JUN, RELA, IL6, etc. GO enrichment analysis mainly involved biological processes such as cytokine receptor binding, heme binding, RNA polymerase Ⅱ transcription factor binding, ubiquitin protein ligase binding, and steroid hormone receptor activity. 149 signal pathways related to Notoginseng Radix et Rhizoma anti-tumor metastasis were obtained by KEGG enrichment analysis, mainly involving multiple signal pathways, such as AGE-RAGE and PI3K-Akt, and hepatitis B, Kaposi's sarcoma-associated herpes virus infection, human cytomegalovirus infection and other viral infections and various tumors. Conclusion:Notoginseng Radix et Rhizoma can pass multiple active components, such as ginsenoside f2, ginsenoside rh2 β-, sitosterol, stigmasterol and quercetin, and multiple targets, such as AKT1, MAPK1, JUN, RELA and IL6, acting on multiple pathways such as PI3K-Akt, thereby playing the role of anti-tumor metastasis.

Objective:To explore the feasibility of mismatch of amide proton transfer weighted (APTw) imaging with diffusion weighted imaging (DWI) in evaluating ischemic penumbra (IP) in patients with wake-up stroke.Methods:A prospective study was performed; 96 patients with wake-up stroke and unilateral middle cerebral artery territory infarction admitted to Emergency Stroke Department, Affiliated Hospital of Jining Medical University from September 2020 to January 2023 were chosen. All patients underwent routine MRI, DWI, APTw imaging and 3D arterial spin labeling (3D-ASL) before treatment and 90 d after treatment. IP presence was defined as changes of abnormal signal on T2-fluid-attenuated inversion recovery (FLAIR) 90 d after treatment greater than 20% of high signal range on DWI before treatment, and it was used as the gold standard to compare the efficacy in evaluating whether the patients had IP based on mismatch of 3D-ASLwith DWI and mismatch of APTw imaging with DWI before treatment. The infarct core (IC) region, mismatch region of APTw imaging with DWI, mismatch region of 3D-ASL with APTw imaging were delineated on the fusion images in patients with IP based on mismatch of 3D-ASLwith DWI and mismatch of APTw with DWI, and the differences of APTw values in different regions were compared.Results:According to the 90-d follow-up results, 50 patients had IP and 46 patients did not have IP. Specificity, accuracy and sensitivity evaluating whether the patients had IP based on mismatch of 3D-ASL with DWI were 86.9%, 93.7% and 100.0%, respectively; specificity, accuracy and sensitivity evaluating whether the patients had IP based on mismatch of APTw imaging with DWI were 100.0%, 95.8% and 92.0%, respectively. The APTw max, APTw min and APTw ave values of the IC region were significantly lower than those of mismatch region of APTw with DWI, and the APTw max-min values of mismatch region of APTw imaging with DWI were significantly higher than those of mismatch region of 3D-ASL with APTw imaging ( P<0.05). Conclusion:APTw imaging can reflect the acidosis status of different brain regions in patients with wake-up stroke; specificity and accuracy evaluating whether the patients have IP based on mismatch of APTw imaging with DWI are higher than those based on mismatch of 3D-ASL with DWI.

Objective:To investigate the role of umbilical cord mesenchymal stem cell-derived exosomes (ucMSC-exos) in acute skin wound healing in mice.Methods:ucMSC-exos were extracted by ultracentrifugation, and identified by transmission electron microscopy, Western blot analysis of exosome surface markers CD63 and TSG101, and particle size analysis. Firstly, in vitro cultured third- to fifth-passage human skin fibroblasts (HSF) were incubated with high-glucose Dulbecco′s modified Eagle′s medium (DMEM) containing 0, 1 and 2 μg/ml exosome suspension for 24 hours (negative control group, 1- and 2-μg/ml groups, respectively) , and cell counting kit-8 (CCK8) assay was performed to evaluate the effect of ucMSC-exos on the proliferative activity of HSF. Secondly, 24 male BALB/c mice aged 8 weeks were selected to construct a mouse model of full-thickness skin wound, and then divided into ucMSC-exos group and phosphate-buffered saline (PBS) group by using a random number table to be subcutaneously injected with exosome suspension and PBS respectively at multiple equidistant sites located about 1 mm apart from the wound edge. On days 0, 4, 7, 10 and 14 after operation, the wounds in mice were observed, and the percentage of residual wound area was calculated in the above two groups. On days 7 and 14 after operation, wound tissues were resected and subjected to hematoxylin and eosin (HE) and Masson staining to observe structural changes of skin tissues. On day 14 after operation, wound tissues were collected in the two groups, and real-time quantitative PCR (qRT-PCR) and Western blot analysis were performed to determine the mRNA and protein expression of type Ⅰ collagen, fibronectin and vascular endothelial growth factor, respectively. Statistical analysis was carried out by using one-way analysis of variance, least significant difference- t test, two-way repeated measures analysis of variance and unpaired t-test. Results:Under the transmission electron microscope, the ucMSC-exos were oval in shape with a diameter of about 100 nm; Western blot analysis showed positive expression of ucMSC-exos surface proteins CD63 and TSG101; particle size analysis showed that 96.2 % of the ucMSC-exos had diameters of 30 - 150 nm. CCK8 assay showed that the relative proliferative activity of HSF was significantly higher in the 1- and 2-μg/ml groups (0.97 ± 0.05, 1.08 ± 0.07, respectively) than in the negative control group (0.71 ± 0.04; t = 2.00, 7.05, respectively, both P < 0.05) , and significantly higher in the 2-μg/ml group than in the 1-μg/ml group ( t = 5.09, P < 0.05) . On days 4, 7, 10 and 14 after operation, the percentage of residual wound area was significantly lower in the ucMSC-exos group than in the PBS group (all P < 0.05) . HE and Masson staining showed increased numbers of hair follicles, glands and granulation tissues, more neovascularization, and neater arrangement of collagens in neonatal skin tissues of the mice in the ucMSC-exos group compared with the PBS group. qRT-PCR and Western blot analysis showed significantly increased mRNA and protein expression of type Ⅰ collagen, fibronectin and vascular endothelial growth factor in the ucMSC-exos group compared with the PBS group (all P < 0.01) . Conclusion:Subcutaneous injections of ucMSC-exos can promote acute skin wound healing in mice, likely by promoting the synthesis of extracellular matrix and vascular endothelial growth factor in wound tissues of mice and proliferation of HSF.

Objective:To observe any effect of intermittent theta burst stimulation (iTBS) on the spatially-delayed responses of working memory using cynomolgus macaques.Methods:The working memory of six male cynomolgus macaques (8-9 years old) was trained using a spatially-delayed response task. They were then randomly divided into an iTBS group and a control group, each of 3. The iTBS group was given iTBS at an intensity of 35% of the maximum output, with 2 seconds of stimulation followed by 8 seconds of rest with trains of 50Hz bursts repeated at a frequency of 5Hz over a period of 192 seconds once daily for 5 days, while the control group was given sham iTBS. Before and after the 5 days, the body weight and working memory of each animal were evaluated. The total number of effective feeding episodes, and of effective feeding episodes with short and long delay periods were recorded.Results:There was no significant change in the average body weight of either group before and after the modeling and iTBS intervention. After the intervention the number of total effective feeding cases and those with a short delay period were both significantly higher in the iTBS group than in the control group. However, no significant inter-group differences in the effective feeding cases with a long delay period were observed.Conclusions:iTBS is effective in improving the spatially-delayed responses of working memory, at least in cynomolgus macaques.

Concrete is the most widely used modern building material. It is easy to crack under the action of stress, which makes the concrete structure permeable, affecting the durability and integrity of the structure, and thus shortening its service life. Microbial in-situ remediation technology is a low cost, effective and green way for concrete crack repairing. Due to its excellent biocompatibility, service life elongation, economic losses and environmental pollution reduction, microbial in-situ remediation technology has been intensively investigated. Bacillus has attracted much attention because of its excellent biomineralization ability, extremely strong environmental tolerance and long-term survival ability of its spores. In order to promote the research, development and large-scale application of microbial in-situ healing of concrete, the paper reviews the mechanism of spore-based in-situ healing of concrete, the survival of spores exposed in concrete, the influence of spores and external additives on the mechanical properties of concrete, progress in research and development of healing agent as well as healing effects. Moreover, future research focuses such as improving the survival ability of spores in the harsh environment of concrete, reducing the influence of external additives on the mechanical properties of concrete, and strengthening the healing effect of actual field applications are also summarized.
Bacillus ; Calcium Carbonate ; Construction Materials ; Spores, Bacterial ; Technology